1. Field of the Invention
The invention relates generally to the fields of autoimmunity and inflammatory bowel disease and more specifically to serological and genetic methods for predicting the responsiveness of clinical subtypes of Crohn's disease to anti-Th1 cytokine therapies such as anti-TNF-.alpha. therapeutics.
2. Background Information
Inflammatory bowel disease (IBD) is the collective term used to describe two gastrointestinal disorders of unknown etiology: Crohn's disease (CD) and ulcerative colitis (UC). The course and prognosis of IBD, which occurs world-wide and is reported to afflict as many as two million people, varies widely. Onset of IBD is predominantly in young adulthood with diarrhea, abdominal pain, and fever the three most common presenting symptoms. The diarrhea may range from mild to severe, and anemia and weight loss are additional common signs of IBD. Ten percent to fifteen percent of all patients with IBD will require surgery over a ten year period. In addition, patients with IBD are at increased risk for the development of intestinal cancer. Reports of an increasing occurrence of psychological problems, including anxiety and depression, are perhaps not surprising symptoms of what is often a debilitating disease that strikes people in the prime of life.
Crohn's disease is a classification representing a number of distinct disease subtypes that affect the gastrointestinal tract and produce similar symptoms. The heterogeneity underlying CD is reflected in variable responses of CD patients to particular treatment strategies: available anti-inflammatory and steroid therapies are effective in treating some patients with CD, while other patients have moderate to severe disease that is refractory to current medical treatment. Anti-Th1 cytokine therapies are a new treatment option for patients with such refractory disease. However, the response to anti-Th1 cytokine therapy, such as an anti-TNF-.alpha. therapeutic, is unpredictable. Although about 65% of those with severe Crohn's disease respond dramatically to anti-Th1 cytokine therapy, the remaining 35% of patients with similar clinical characteristics demonstrate a small or negligible response.
Methods for predicting whether a patient with CD will respond to anti-Th1 cytokine therapy would represent a major clinical advance that would aid in the therapeutic management of CD. Such methods would be advantageous in saving the cost of treating those having an unresponsive subtype of CD and would eliminate the disappointment of those needlessly undergoing such therapy. Such methods also would advance medical management of CD by identifying a subgroup of non-responsive patients for whom alternative treatment modalities must be sought. Unfortunately, methods of stratifying CD into clinical subtypes having predictable responses to anti-Th1 cytokine therapy are currently not available. Thus, there is a need for such methods. The present invention satisfies this need and provides related advantages as well.